Review Microbiota of the Tongue and Systemic Connections: The Examination of the Tongue as an Integrated Approach in Oral Medicine Cinzia Casu 1,* , Giovanna Mosaico 2,* , Valentino Natoli 3,4 , Antonio Scarano 5, Felice Lorusso 5 and Francesco Inchingolo 3 1 Department of Surgical Sciences, Oral Biotechnology Laboratory (OBL), University of Cagliari, 09126 Cagliari, Italy 2 RDH, Freelancer Researcher, 72100 Brindisi, Italy 3 DDS, Private Dental Practice, 72015 Fasano, Italy; [email protected] (V.N.); [email protected] (F.I.) 4 Department of Interdisciplinary Medicine, University of Medicine Aldo Moro, 70124 Bari, Italy 5 Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy; [email protected] (A.S.); [email protected] (F.L.) * Correspondence: [email protected] (C.C.); [email protected] (G.M.); Tel.: +39-070-609-2294 (C.C.) Abstract: The tongue is able to quickly reflect the state of health or disease of the human body. Tongue inspection is an important diagnostic approach. It is a unique method that allows to explore the pathogenesis of diseases based on the guiding principles of the holistic concept that involves the observation of changes in the lining of the tongue in order to understand the physiological functions and pathological changes of the body. It is a potential method of screening and early detection of cancer. However, the subjective inspection of the tongue has a low reliability index, and therefore computerized systems of acquisition of diagnostic bioinformation have been developed to analyze Citation: Casu, C.; Mosaico, G.; the lining of the tongue. Next-generation sequencing technology is used to determine the V2–V4 Natoli, V.; Scarano, A.; Lorusso, F.; Inchingolo, F. Microbiota of the hypervariable regions of 16S rRNA to study the microbiota. A lot of neoplasms are identified only at Tongue and Systemic Connections: an advanced phase, while in the early stages, many subjects remain in an asymptomatic form. On The Examination of the Tongue as an the contrary, the early diagnosis is able to increase the prognosis of cancer and improve the survival Integrated Approach in Oral rates of subjects. Evidently, it is necessary to develop new strategies in oral medicine for the early Medicine. Hygiene 2021, 1, 56–68. diagnosis of diseases, and the diagnosis of the tongue as a minimally invasive method is certainly https://doi.org/10.3390/ one of them. hygiene1020006 Keywords: tongue microbiota; host–microbiota symbiosis; tongue diagnosis; systems correlations; Received: 27 April 2021 minimally invasive; hygiene Accepted: 25 June 2021 Published: 1 July 2021 Publisher’s Note: MDPI stays neutral 1. Introduction with regard to jurisdictional claims in published maps and institutional affil- For thousands of years, doctors have diagnosed a patient’s health by inspecting the iations. tongue, especially the back of the tongue. Inspection of the tongue as a method of clinical diagnosis is a unique feature of Traditional Chinese Medicine (TCM). The tongue inspection is a procedure that has been reported from the Shang Dynasty (from 1600 BC to 1000 BC) that should be performed by the clinical observation the tongue body to evaluate its morphological and color homogeneity. In accordance to the Traditional Copyright: © 2021 by the authors. Chinese Medicine, the tongue is able to absolve a key role of a biosensor, while the different Licensee MDPI, Basel, Switzerland. tongue regions are able to provide information to check the diagnosis the organ systems This article is an open access article distributed under the terms and health [1,2]. conditions of the Creative Commons In accordance to Traditional Chinese Medicine, “A pathology arises associated to Attribution (CC BY) license (https:// a tongue surface coating appearance. The surface coating represents the exterior mani- creativecommons.org/licenses/by/ festation, which corresponds to the sustaining disease, and is the primary indication for 4.0/). the diagnosis making”. In this way, the appropriate knowledge of the molecular aspects Hygiene 2021, 1, 56–68. https://doi.org/10.3390/hygiene1020006 https://www.mdpi.com/journal/hygiene Hygiene 2021, 1 57 Hygiene 2021, 1, FOR PEER REVIEW 2 of tongue response is a key factor to comprehend this semeiotic medical practice [1,3,4]. Several studies on the microbiology of the healthy human tongue, through the sequenc- ing of 16S rRNA, which is applied for the detection, categorization, and evaluation of themanifestation, microbic which charge corresponds within theto the biological sustaining disease, mixtures, and is have the primary shown indication that the most abundant for the diagnosis making”. In this way, the appropriate knowledge of the molecular phylaaspects areof tongueFusobacteria response, Actinobacteriais a key factor to, comprehendFirmicutes, thisProteobacteria semeiotic medical, and practice Bacteroidetes [1,4,5]. The variation[1,3,4]. Several in the studies microbiota on the microbiolo of the tonguegy of the lining healthy recorded human tongue, by metagenomic through the sequencing iden- tifiessequencing potential of 16S biomarkersrRNA, which is for applied several for the diseases, detection, including categorization, the and precancerous evaluation cascade [1,6,7]. Theof the thin microbic white charge or within reddish the biological tongue mixtures, coating have with shown 0/1 that patina the most is aabundant symbol of good health phyla are Fusobacteria, Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes [1,4,5]. The (Figuresvariation 1in and the 2microbiota) , while of the the “white-fat” tongue lining and recorded “yellow-dense” by metagenomic coating sequencing (Figures 3 and4) may beidentifies an indication potential ofbiomarkers inflammation, for several infection, diseases, andincluding stress, the asprecancerous well as of cascade immune and endocrine disorders[1,6,7]. The thin (Figure white5 or)[ reddish8,9]. Thicktongue coatin coatg and with tongue 0/1 patina moisture is a symbol are of good increased health in tumors. The relationships(Figures 1 and 2), between while the “white-fat” tongue diagnosis and “yellow-dense” and diseases, coating including (Figures 3 and rheumatoid 4) may arthritis, gas- be an indication of inflammation, infection, and stress, as well as of immune and tritis and precancerous lesions, liver, pancreatic, and lung cancer, were explored [1,10–15]. endocrine disorders (Figure 5) [8,9]. Thick coat and tongue moisture are increased in Tongue-liningtumors. The relationships microbiota between biomarkers tongue diagnosis could and provide diseases, a complement including rheumatoid for the diagnosis of sev- eralarthritis, diseases gastritis from and the precancerous noninvasive, lesions, individualized, liver, pancreatic, and and long-term lung cancer, monitoring were aspects [1,16]. Tongueexplored diagnosis[1,10–15]. Tongue-lining is a simple, microbiota noninvasive biomarkers method could of provide assessing a complement physiological for conditions by observingthe diagnosis the of thicknessseveral diseases and colorfrom the of noninvasive, the coating individualized, [6]. The tongue and coatinglong-term is categorized into monitoring aspects [1,16]. Tongue diagnosis is a simple, noninvasive method of assessing threephysiological different conditions classes by in observing accordance the th toickness their and color color typologies: of the coating white [6]. The coating (W), yellow coatingtongue coating (Y), and is categorized black and into gray three coating different (Table classes1). Ain yellowaccordance coat to is their considered color an indication oftypologies: water retentionwhite coating and (W), heat yellow [3 coating]. The (Y), most and black common and gray syndromes coating (Table are 1).the A following four: externalyellow coat cold is considered syndrome, an indication internal of water cold retention syndrome, and heat external [3]. The heatmost common syndrome, and internal syndromes are the following four: external cold syndrome, internal cold syndrome, heatexternal syndrome, heat syndrome, and and are internal associated heat sy withndrome, thin and white,are associated thick with white, thin thinwhite, yellow, and thick yellowthick white, tongue thin yellow, coatings and [ 1thick]. Cold yellow and tongue hot syndromes coatings [1]. Cold are two and contraryhot syndromes but internally related conditionsare two contrary [8]. but According internally related to the condit TCMions theory, [8]. According the tongue to the TCM is an theory, external the extension of the spleentongue is and an external stomach extension [17,18 of]. the Western spleen and medicine stomach [17,18]. refers Western to the indexesmedicine refers of the thickness of the coatto the on indexes theback of the ofthickness the tongue, of the coat classifying on the back it of in the four tongue, degrees classifying [19] (Tableit in four2). degrees [19] (Table 2). Hygiene 2021, 1, FOR PEER REVIEW 3 FigureFigure 1. 1. StrawberryStrawberry tongue tongue health healthsymbol with symbol thin coat with (TCM), thin coatgrade (TCM),0/1 according grade to Miyazaki. 0/1 according to Miyazaki. FigureFigure 2. 2. ThinThin white white tongue tongue (TCM), (TCM), grade 2 according grade 2 to according Miyazaki. to Miyazaki. Figure 3. Thick white and yellow tongue (TCM), grade 3 according to Miyazaki. Figure 4. Yellow fat tongue (TCM), grade 2 according to Miyazaki. Hygiene 2021, 1, FOR PEER REVIEW 3